Trypanosomatids are a group of kinetoplastid protozoa distinguished by having only a single flagellum. Trypanosomatids are responsible for diseases such as South American trypanosomiasis (Chagas Disease) and African Animal Trypanosomosis (AAT).
Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is endemic to many countries in Latin America. The World Health Organization has estimated that 16-18 million people are currently infected and 90 million are at risk of acquiring the infection (WHO 2002, Schofield et al, 2006). The estimated global burden of the disease is 649,000 disability adjusted life years (the number of healthy years of life lost due to premature death and disability). Causing about 14,000 deaths annually, Chagas disease kills more people in Latin America than any other parasitic disease, including malaria.
T. cruzi is transmitted by various insect vectors that belong to the Reduviidae family. Transmission to humans is dependent on living conditions as these insects inhabit houses of mud and thatch which are common in lower socioeconomic areas. Infection may also be acquired by consuming contaminated food, congenitally, or via blood transfusion or organ transplantation. The acute phase of T. cruzi infection is generally controlled by the emerging immune response and is mild or asymptomatic and thus often undetected. However, the vast majority of infected individuals fail to clear the infection and thus remain chronically infected; 30-40% of these will eventually develop life-threatening heart or gastrointestinal disease. Chronic Chagas remains an incurable disease that causes long term severe disability or death in approximately one-third of infected individuals. In addition, disability caused by chronic Chagas disease has a great social and economic impact, including unemployment and decreased earning ability. From a 2012 estimate by the World Health Organization, over 500,000 Disability-Adjusted Life Years (DALYs) were attributable to Chagas disease (Moncayo A, Ortiz Yanine M. Ann Trop Med Parasitol. 2006; 100:663-677). In addition to the loss in productivity, the medical costs to treat infected individuals who develop severe cardiac or chronic digestive problems are high.
It has long been established that T. cruzi can infect dogs, particularly those who are housed outdoors in the southern US, Central, and South America. A recent study in Texas suggested that shelter dogs serve as a good sentinel for all dogs, and found that −9% of shelter dogs evaluated across Texas harbored T. cruzi. In Texas, T. cruzi infection in dogs is considered a “notifiable condition”—any dog found to be harboring the parasite must be reported to the Texas Department of State Health Services. As there is no approved treatment for Chagas disease in dogs, animals may be euthanized.
African animal trypanosomosis is endemic to 37 African countries, affecting livestock on 10 million km2 of arable land and remains a major constraint to agricultural production, in particular livestock production in these areas. Trypanosomosis is also prevalent in Central and South America. The disease is caused primarily by three protozoan parasites: Trypanosoma congolense (T. congolense), T. vivax and T. evansi, and is vectored by the tsetse fly and, for T. evansi, also mechanically transferred from host to host by the tabanus spp. of biting fly. The disease is characterized by progressive anemia, loss of condition and lassitude with recurrent episodes of fever and parasitemia. The severity of the disease varies with Trypanosoma species, breed, age and health status of the infected animal. In cattle, this infection causes major mortality and morbidity with significant negative effects on growth, lactation, weaning age, and weight. In draught animals the power, speed and distance covered per day is also impacted. Trypanosomosis has a major economic impact on cattle production in Africa and, if untreated, generally results in chronic illness with high mortality. Trypanosomosis has been estimated to cost African livestock farmers US $2 to 5 billion per annum. In the absence of vaccines, control of this disease has for long been focused on chemotherapy and vector control. For many decades only three compounds, diminazene, isometamidium, and homidium, have been widely used as trypanocides, and consequently drug resistance in the target pathogens has become a major concern. Novel chemical entities with novel mechanisms of action are urgently needed to combat these diseases.